1. Field of the Invention
The present invention relates to substrata to be employed for culturing cells controlling at least one of the cellular functions, i.e., adhesion, proliferation, differentiation, survival, maintenance of undifferentiated state, and apoptosis. The present invention also relates to production methods of the same, cell culture methods and cell culture apparatuses using the same. More particularly, the invention relates to a substratum onto which a substance that affects at least one of the above cellular functions is immobilized by means for ejecting fine droplets, a production method of the same, and a method for cell culture using the same. Also, the invention relates to a method of cell culture controlling cell proliferation or differentiation using a substance that affects at least one of them, as well as to a substratum for cell culture suitable to be used for this method, a production method of the substratum and a cell culture apparatus.
2. Related Background Art
Recently, animal and plant cell cultivation under various conditions or metabolic products thereof are very actively studied, especially, production of substances of which chemical synthesis are impossible or very difficult are investigated in various fields utilizing certain cell activities.
On the other hand, with rapid progress in cell engineering and medical engineering, microbiosensors, artificial organs, and also neuron computers using cells have drawn attentions, and are under active development. The substance that affects a cellular function such as cell adhesion, proliferation, differentiation, survival, maintenance of undifferentiated state and apoptosis may be different depending on individual cells, and in many cases, a plurality of substances affect a certain cellular function in combination. Thus, in order to carry out cell culture while controlling these functions, it is indispensable to specify culture conditions including substances to be used, their combinations and proportions.
U.S. Pat. No. 5,108,926 discloses a cell positioning method to form patterns of cell-adhesion proteins on a substrate with an ink jet printer, and apparatuses for it.
Also, a report (Biotechnol. Prog., 12, 700-702, (1996)) studies effect of cell growth factors that affect cell proliferation and differentiation by immobilizing them on a substrate using photolithography.
Japanese Patent Application Laid-Open No. 2000-512009, discloses a method of cell screening by immobilizing substances that affect cell adhesion properties on a substrate. It teaches that reactive functional groups are introduced onto the substrate and the cell-adhesion substance is immobilized to the substrate via a divalent cross-linking agent. Photolithography was used to bond the functional group and the cell-adhesive substance.